Nonspecific adsorption inhibitor of substance relating to living body and method for coating article

Abstract

A nonspecific adsorption inhibitor of a substance relating to a living body, which inhibits nonspecific adsorption of a substance relating to a living body such as various species of proteins which are used in clinical diagnostic agents, clinical diagnosis devices, biochips and the like, and a method for coating an article using said nonspecific adsorption inhibitor.

What is claimed is: 
     
       1. A method of inhibiting the adsorption of lipids and/or proteins to an article, comprising:
 (1) allowing the article to contact an aqueous solution comprising a water-soluble copolymer, wherein the water-soluble copolymer comprises: 
 (i) a repeating unit (A) derived from at least one species of monomer (a) and represented by formula (1): 
 
       
         
           
           
               
               
           
         
         wherein R 0  represents a hydrogen atom or a methyl group and Z represents a group represented by formula (1a) or (1b): 
       
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  independently represent a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms or an alkyl group having from 1 to 8 carbon atoms which is substituted with at least one group selected from a hydroxyl group, a carboxyl group, an alkoxy group, an acyloxy group and an alkoxycarbonyl group; 
       
       
         
           
           
               
               
           
         
         wherein R 3  and R 4  independently represent single bond, methylene, methylene substituted with a hydroxyl group or a carboxyl group, an alkylene group having from 2 to 7 carbon atoms or an alkylene group having from 2 to 7 carbon atoms substituted with a hydroxyl group or carboxyl group wherein total number of carbon atoms of R 3  and R 4  is from 4 to 10; wherein at least one of R 3  and R 4  may have an ether bond, and Y represents any one of a single bond, O and S; and 
         (ii) a repeating unit (B) derived from at least one species of a monomer (b) and represented by formula (2): 
       
       
         
           
           
               
               
           
         
         wherein R 5  represents a hydrogen atom or a methyl group; and 
         R 6  represents phenyl group or a group represented by —CO 2 R 7  wherein R 7  represents an unsubstituted alkyl group having from 1 to 12 carbon atoms, an alicyclic hydrocarbon, an aromatic hydrocarbon, or an alkyl group having from 1 to 12 carbon atoms substituted with a hydroxyl group or carboxyl group, 
         wherein the amount of monomer (a) in the water-soluble copolymer is 30 to 99% by weight and the amount of monomer (b) in the water-soluble copolymer is 1 to 70% by weight; and 
         (iii) a repeating unit (C) represented by the following formula (3): 
       
       
         
           
           
               
               
           
         
       
       wherein
 R 8  represents a hydrogen atom or a methyl group and 
 R 9  represents an organic group which comprises at least one aldo group or keto group a formyl group, a formylphenyl group, a group presented by formula (4), a group represented by formula (5), an acetyl group, an acetylphenyl group, a group represented by formula (6) or a group represented by formula (7): 
 
       
         
           
           
               
               
           
         
         wherein R 10  to R 13  are independently a hydrogen atom, a methyl group or an ethyl group; 
       
       
         
           
           
               
               
           
         
         wherein R 14  to R 17  are independently a hydrogen atom, methyl group or ethyl group; 
       
       
         
           
           
               
               
           
         
         wherein R 18  to R 21  are independently a hydrogen atom, a methyl group or an ethyl group; 
       
       
         
           
           
               
               
           
         
         wherein R 22  to R 25  are independently a hydrogen atom, a methyl group or an ethyl group; followed by 
         (2) contacting the article with at least one lipid, protein or a mixture thereof, wherein the copolymer inhibits nonspecific adsorption of lipids and proteins to the article. 
       
     
     
       2. The method of  claim 1 , wherein R 1  represents a hydrogen atom or a methyl group and R 2  represents at least one species selected from a hydrogen atom, a methyl group and a hydroxyethyl group. 
     
     
       3. The method of  claim 2 , wherein repeating unit (B) is derived from at least one monomer having a solubility in water of less than 20%. 
     
     
       4. The method of  claim 1 , wherein repeating unit (B) is derived from at least one monomer having a solubility in water of less than 20%. 
     
     
       5. The method of  claim 1 , wherein
 R 5  represents a hydrogen atom or a methyl group; 
 R 6  represents —CO 2 R 7 ; and 
 R 7  represents at least one species selected from a methyl group, ethyl group and methoxyethyl group. 
 
     
     
       6. The method of  claim 1 , wherein the water-soluble copolymer is reacted with at least one a hydrazide compound (H) that comprises at least two hydrazino groups per one molecule; and wherein the water-soluble copolymer is crosslinked by the reaction of a hydrazino group with a keto and/or aldo group of the water-soluble copolymer. 
     
     
       7. The method of  claim 6 , wherein the hydrazide compound comprises at least one member selected from the group consisting of (1) dicarboxylic hydrazides having from 2 to 10 carbon atoms in total, (2) hydrazides having three or more functional groups, (3) water-soluble dihydrazides and (4) a compound in which at least a part of the hydrazine groups of a multifunctional hydrazine derivative is blocked by allowing them to react with a carbonyl compound. 
     
     
       8. The method of  claim 1 , wherein the adsorption of lipids to the article is inhibited. 
     
     
       9. The method of  claim 1 , wherein the adsorption of proteins to the article is inhibited. 
     
     
       10. The method of  claim 1 , wherein the adsorption of an antibody to the article is inhibited. 
     
     
       11. The method of  claim 1 , wherein the water-soluble copolymer is adhered to the article through the hydrophobic bond of the repeating unit (B). 
     
     
       12. The method of  claim 1 , wherein the amount of monomer (a) in the water-soluble copolymer is 40 to 95% by weight and the amount of monomer (b) in the water-soluble copolymer is 5 to 60% by weight. 
     
     
       13. The method of  claim 1 , which comprises contacting the article with at least one lipid. 
     
     
       14. The method of  claim 1 , which comprises contacting the article with at least one protein. 
     
     
       15. The method of  claim 14 , wherein the protein is an antibody. 
     
     
       16. The method of  claim 1 , wherein the article is a biochip. 
     
     
       17. The method of  claim 1 , wherein the article is composed of polystyrene. 
     
     
       18. The method of  claim 1 , wherein the article is a polystyrene plate containing wells. 
     
     
       19. The method of  claim 1 , further comprising, between (1) and (2), washing the article with water.